A phase II pilot trial has explored the use of very low doses of rituximab in treating autoimmune hemolytic anemia (AIHA). Researchers at the Medical University of Vienna investigated the effects and safety of administering rituximab at doses significantly lower than typically used, aiming to suppress CD20+ cell counts effectively. The study, published in Frontiers in Medicine, highlights the transient depletion of CD20+ cells but the failure to achieve sustained suppression with the tested regimens.
The open-label trial included ten patients with various forms of AIHA (7 with cold agglutinin disease, 2 with warm AIHA, and 1 with mixed-type AIHA). The patients received rituximab at very low doses: 5mg/m² every three weeks, 20mg every four weeks, 50mg every three months, and 100mg every three months. The primary goal was to assess the impact of these low doses on CD20+ cell depletion.
Initial Depletion vs. Sustained Suppression
The initial infusion of rituximab led to a depletion of >95% of CD20+ cells in nearly all patients. However, the study revealed that these low-dose regimens were ineffective in maintaining sustained CD20+ cell depletion. CD20+ cells recovered with considerable interindividual variability, indicating that the low doses could not provide lasting suppression.
Researchers found that CD20+ lymphocytes remained below the detection limit when rituximab plasma concentrations exceeded 0.4µg/mL. This observation suggests a potential threshold for rituximab concentration necessary to maintain CD20+ cell suppression.
Implications and Future Directions
According to the study, rituximab doses as low as 5mg/m² can transiently deplete CD20+ cells in most patients. However, the tested low-dose regimens were unable to permanently suppress these cells. The empirically identified EC95% of 0.4µg/mL rituximab may inform future studies exploring low-dose rituximab strategies.
The authors suggest that this concentration level could serve as a guide for future research aiming to optimize low-dose rituximab protocols. Further studies are needed to determine the optimal dosing strategies for achieving sustained CD20+ cell depletion in AIHA patients while minimizing potential side effects and costs associated with higher doses.
